In response to RFA-AA-12-006, this application proposes the Administrative Component of the National Consortium on Alcohol and Neurodevelopment in Adolescence (N-CANDA), located at UCSD, to determine the effects of alcohol use on the developing adolescent brain. This consortium was designed to provide a nationally representative sample of adolescents and to integrate the diverse scientific expertise and research experience with youth represented by researchers at each site. As such, the following applications should be considered jointly: N-CANDA: Administrative Component, UCSD (PI: Sandra Brown PhD (Contact), Susan Tapert PhD) N-CANDA: Data Component, SRI (PI: Adolf Pfefferbaum, M.D.) N-CANDA: Duke (PI: Michael DeBellis, M.D.) N-CANDA: Pittsburgh (PI: Duncan Clark, Ph.D., M.D.) N-CANDA: SRI (PIs: Ian Colrain, Ph.D. (Contact) and Fiona Baker, Ph.D.) N-CANDA: UCSD (PI: Susan Tapert, Ph.D.) Recruited at ages 12 through 21, a high-risk enhanced community sample of 680 subjects will complete a baseline assessment then undergo three annual follow-up assessments in an accelerated longitudinal design. At each visit, a multimodal MRI protocol, comprehensive neuropsychological battery, and assessment of alcohol use and related problems, along with other substance involvement, mental health symptoms, and other risk factors, will be measured. Brain imaging uses state-of-the-art high-resolution structural MRI (sMRI), diffusion tensor imaging (DTI), resting state MRI (rsMRI), and an anti-saccade or Stroop functional MRI task to capitalize on local expertise. The examination of alcohol consequences will focus on structural and functional maturation of brain areas that are actively developing during adolescence, involved in psychological regulation, responsive to rewards, and thought to be vulnerable to toxic alcohol effects. Five aims specified in the RFA will be systematically tested with a focus on adolescent substance use and neuromaturational trajectories. Each of the four Research Components will collaborate with another site on two additional aims. Examined in the context of risks and baseline brain characteristics, we will determine both the effects of alcohol exposure on the developmental trajectory of the adolescent human brain, and identify preexisting psychobiological vulnerabilities that may put an adolescent at greater risk for an alcohol use disorder. PUBLIC HEALTH RELEVANCE: Successful completion of the above aims will demonstrate that adolescent alcohol involvement disrupts brain development. This project represents a critical step in understanding neurobiological risks for accelerated alcohol use and alcohol effects on brain development in adolescence.